Expression of BCL10 in cervical cancer has a role in the regulation of cell growth through the activation of NF-κB‐dependent cyclin D1 signaling

ObjectiveWe recently characterized the molecular linkage that directs both BCL10 overexpression and nuclear translocation in response to inflammation-related NF-κB signaling pathway. Since NF-κB activation has been shown to occur in the pathogenesis of cervical cancer, we sought to investigate whether BCL10 possesses clinical significance in relation to cervical cancer.MethodsFour cervical cancer cell lines (C33A, SiHa, HeLa, and CaSki) were used in this study. The DNA-binding activity of NF-κB was determined by the luciferase assay. The expression of BCL10, NF-κB, and cyclin D1 in tumor cells from an array of 182 tissue samples was examined using immunohistochemical staining.ResultsWe transfected four cervical cancer cell lines with BCL10 small interfering RNA (siRNA), and discovered that the down-regulation of BCL10 inhibited the viability of these cervical cancer cells through G1 arrest. BCL10 siRNA treatment inhibited the expression of p-IKKβ and p-IκB, and also down-regulated both NF-κB activation cyclin D1, its downstream cell cycle protein. Our results reveal that cervical cancer had a higher rate of positive cytoplasmic staining (74.1%, 123/166) than either carcinoma in situ (50.0%, 3/6) or normal cervix (0.0%, 0/10); and that poorly differentiated cancer had a higher rate of cytoplasm staining (80.7%, 71/88) than moderately differentiated (75.4%, 43/57) and well differentiated (40%, 4/10) carcinoma. Furthermore, nuclear expression of BCL10 was closely associated with NF-κB activation (p < 0.001) and cyclin D1 expression (p < 0.001).ConclusionsOur findings indicate that BCL10 plays an important role in controlling the growth of cervical cancer cells through NF-κB dependent cyclin D1 regulation.

► The BCL10/NF-κB/cyclin D1 signaling pathway is involved in the molecular pathogenesis of cervical cancer.
► BCL10 expression is associated with both an aggressive histologic classification and the expression of either NF-κB or cyclin D1.
► The development of novel BCL10-related therapeutic strategies for cervical cancer is warranted.